April 16, 2018

Recently I was having an email exchange with a friend (a prominent public intellectual who is not a scientist), and we were thinking about what “ancestral Africans” looked like. More precisely, the populations which were resident around ~100,000 to ~200,000 years before the present. These are the people who are depicted in paleoanthropology documentaries. Here were some of my major contentions:

1) We don’t know what they looked like
2) They probably were more likely to look like modern Africans than non-Africans
3) But modern Africans are diverse in their looks and we could expect that ancient Africans were too

The neighbor-joining tree above is generated with a naive model of successive bifurcation.

1) Khoisan split off 200,000 years ago
2) Mbuti split off 150,000 years ago
3) Mende split off 100,000 years ago
4) Japanese about 50,000 years ago
5) While Pathan and Basque only 15,000 years ago

The model is wrong in the details. Pathan and Basque have some ancestry is which recently diverged, and much that is deeply diverged. The 15,000 year value is just an average. Similarly, the Khoisan have some Eurasian ancestry. But in the broad sketch it illustrates that some African populations diverged a very long time ago from other groups.

Ancient Africans date to ~200,000 years before the present for all the modern populations. Khoisan to Japanese. You could probably use phylogenetic character reconstruction methods to attempt to infer what ancient Africans looked like…but I’m not sure that it would be useful since modern humans have spread over so many ecologies over such a short span of time.

Outside of Sub-Saharan Africa perhaps on the order of 95% of the ancestry derives from an expansion from a small founder group between 60 and 80 thousand years ago. Removing the “Basal Eurasian” component, groups as diverse as Native Americans, Oceanians and East Asians probably derive their ancestry from a common group which flourished between 50 and 60 thousand years ago (this pulse is the majority of the ancestry of Europeans and South and West Asians as well).

The point here is to illustrate that 50,000 years is definitely sufficient for a great deal of diversity to have emerged in human physical variation. And yet the Khoisan are ~200,000 years diverged from their ancestors within Africa. We actually know that indigenous southern Africans have been selected for lighter pigmentation. We also know that loci associated with pigmentation in modern humans exhibits a lot of variation in Africans, and this variation is likely an ancestral feature of our species.

In sum, the number of generations between ancestral Africans and all modern descendent populations is great enough that I’m not uncertain that we can predict what they look like in anything except their skeletal features. Additionally, most of the history of anatomically modern humans was likely highly structured within Africa. That’s another way of saying that ancient Africans themselves were probably physically diverse.

With all that being said, all things equal ancient Africans probably are more likely to look like modern Africans than modern non-Africans. The main reason is simply that modern Africans occupy the same broad ecological landscape as ancient Africans, and many of our features, from our build to our complexion seem dependent upon environmental pressures. There’s lot of evidence that very light skin is probably a derived characteristic of our species (there are consistent signatures of sweeps around pigmentation loci). And, there is also evidence that some of the archaic introgression into non-Africans may have consequences in our morphology and external physical characteristics. For example, Eurasians seem to have very high frequencies of Neanderthal variants of the keratin gene. This is implicated in hair, skin and nail development.

Addendum: Note that even if we have ancient genomes, polygenic characteristics are still hard to predict. Even today common SNPs only explain a minority of the variation in hair color in Europeans.

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October 11, 2017

Very interesting abstract at the ASHG meeting of a plenary presentation,Novel loci associated with skin pigmentation identified in African populations. This is clearly the work that one of the comments on this weblog alluded to last summer during SMBE. There I was talking about the likely introduction of the derived SLC24A5 variant to the Khoisan peoples and its positive selection in peoples in southern Africa.

Below is the abstract in full. Those who follow the literature on this see the usual suspects in relation to genes, but also new ones:

Despite the wide range of variation in skin pigmentation in Africans, little is known about its genetic basis. To investigate this question we performed a GWAS on pigmentation in 1,593 Africans from populations in Ethiopia, Tanzania, and Botswana. We identify significantly associated loci in or near SLC24A5, MFSD12, TMEM138…OCA2 and HERC2. Allele frequencies at these loci in global populations are strongly correlated with UV exposure. At SLC24A5 we find that a non-synonymous mutation associated with depigmentation in non-Africans was introduced into East Africa by gene flow, and subsequently rose to high frequency. At MFSD12, we identify novel variants that are strongly correlated with dark pigmentation in populations with Nilo-Saharan ancestry. Functional assays reveal that MFSD12 codes for a lysosomal protein that influences pigmentation in cultured melanocytes, zebrafish and mice. CRISPR knockouts of murine Mfsd12 display reduced pheomelanin pigmentation similar to the grizzled mouse mutant (gr/gr). Exome sequencing of gr/gr mice identified a 9 bp in-frame deletion in exon two of Mfsd12. Thus, using human GWAS data we were able to map a classic mouse pigmentation mutant. At TMEM138…we identify mutations in melanocyte-specific regulatory regions associated with expression of UV response genes. Variants associated with light pigmentation at this locus show evidence of a selective sweep in Eurasians. At OCA2 and HERC2 we identify novel variants associated with pigmentation and at OCA2, the oculocutaneous albinism II gene, we find evidence for balancing selection maintaining alleles associated with both light and dark skin pigmentation. We observe at all loci that variants associated with dark pigmentation in African populations are identical by descent in southern Asian and Australo-Melanesian populations and did not arise due to convergent evolution. Further, the alleles associated with skin pigmentation at all loci but SLC24A5 are ancient, predating the origin of modern humans. The ancestral alleles at the majority of predicted causal SNPs are associated with light skin, raising the possibility that the ancestors of modern humans could have had relatively light skin color, as is observed in the San population today. This study sheds new light on the evolutionary history of pigmentation in humans.

Much of this is not surprising. Looking at patterns of variation around pigmentation loci researchers suggested years ago that Melanesians and Africans exhibited evidence of similarity and functional constraint. That is, the dark skin alleles date back to Africa and did not deviate from their state due to selection pressures. In contrast, light skin alleles in places like eastern and western Eurasia are quite different.

Nyakim Gatwech

This abstract also confirms something I said in a comment on the same thread, that Nilotic peoples are the ones likely to have been subject to selection for dark skin in the last 10,000 years. You see above that variants on MFSD12 are correlated with dark complexion. In particular, in Nilo-Saharan groups. The model Nyakim Gatwech is of South Sudanese nationality and has a social media account famous for spotlighting her dark skin. In comparison to the Gatwech and the San Bushman child above are so different in color that I think it would be clear these two individuals come from very distinct populations.

The fascinating element of this abstract is the finding that most of the alleles which are correlated with lighter skin are very ancient and that they are the ancestral alleles more often than the derived! We’ll have to wait until the paper comes out. My assumption is that after the presentation Science will put it on their website. But until then here are some comments:

There is obviously a bias in the studies of pigmentation toward those which highlight European variability.

The theory of balancing selection makes sense to me because ancient DNA is showing OCA2 “blue eye” alleles which are not ancestral in places outside of Western Europe. And in East Asia there their own variants.

Lots of variance in pigmentation not accounted for in mixed populations (again, lots of the early genomic studies focused on populations which were highly diverged and had nearly fixed differences). Presumably, African research will pick a lot of this up.

This also should make us skeptical of the idea that Western Europeans were necessarily very dark skinned, as now we know that human pigmentation architecture is complex enough that sampling modern populations expand our understanding a great deal.

Finally, it’s long been assumed that at some stage early on humans were light skinned on most of their body because we had fur. When we lost our fur is when we would need to have developed dark skin. This abstract is not clear at how far long ago light and dark alleles coalesce to common ancestors.

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November 7, 2011

That query doesn’t seem to have an easy answer on Google, so I’m trying to enter it here. A prominent genomicist asserted a ballpark figure of ~30,000 human genomes in the year 2011. Most of that is in the year 2011 itself. Also, in regards to the “$1,000 genome” question, it seems that some labs can get $4,000 dollar human genomes if they buy in bulk (50 at a time). The price point can even go lower apparently, though no number was divulged. This isn’t going to be the “retail” price point obviously, but we’re probably at most an order of magnitude away from the $1,000 genome as of now. We were also told of the likelihood of the $100 genome, in today’s dollars, in 2020.